PTEN is recognized as a prognostic-related biomarker and inhibits proliferation and invasiveness of skull base chordoma cells.

Objective: This work aimed to examine the function of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in skull base chordoma (SBC) at the clinical and cellular levels. Methods: Totally 65 paraffin-embedded and 86 frozen specimens from 96 patients administered surgery were analyzed. Immunohistochemical staining and quantitative real-time polymerase chain reaction were performed, and the associations of PTEN expression with clinical features were assessed. At the cellular level, PTEN was knocked down by the siRNA approach in the UCH-1 cell line, and cell proliferation and invasion were detected by the CCK-8 and migration assays, respectively. Results: At the protein level, PTEN expression was increased in non-bone-invasive tumor samples in comparison with bone-invasive specimens (p = 0.025), and elevated in soft SBCs in comparison with hard tumors (p = 0.017). Increased PTEN protein expression was associated with decreased risk of tumor progression (p = 0.002; hazard ratio = 0.981, 95% confidence interval: 0.969-0.993). At the gene expression level, the cut-off value was set at 10.5 after ROC curve analysis, and SBC specimens were divided into two groups: PTEN high group, ΔCt value below 10.5; PTEN low group, ΔCt value above 10.5. In multivariate regression analysis of PFS, the risk of tumor progression was increased in PTEN low group tumors in comparison with PTEN high group SBCs (p = 0.006). In the CCK-8 assay, in comparison with control cells, PTEN knockdown cells had increased absorbance, suggesting elevated cell proliferation rate. In the invasion assay, the number of tumor cells penetrating into the lower chamber was significantly increased in the PTEN knockdown group compared with control cells. Conclusions: Decreased PTEN expression in SBC, at the protein and gene levels, is associated with reduced PFS. PTEN knockdown in chordoma cells led to enhanced proliferation and invasiveness.

Clinical study on acupuncture treatment of gastrointestinal damp-heat acne.

BACKGROUND: Acne is a common inflammatory disease of sebaceous glands, which brings extensive emotional and psychological distress to patients. Although acupuncture has certain advantages in the treatment of acne, the curative effect is not exact. The purpose of this trial is to evaluate the feasibility, preliminary efficacy, and safety of the "Spleen and Stomach Guiyuan Acupuncture Method" (SSGA) in the treatment of gastrointestinal damp-heat acne. METHODS: The proposed protocol is planned as a randomized, assessor-blind, conventional-treatment-controlled trial to evaluate the efficacy of SSGA on gastrointestinal damp-heat acne. Seventy six gastrointestinal damp-heat acne patients will be randomly divided into 2 groups and receive SSGA or conventional acupuncture treatment. The entire study period is 12 weeks, including an 8-week treatment period and a 4-week follow-up period. All patients will receive 16 sessions of acupuncture treatment over 8 weeks. The primary outcome is the investigation global assessment (IGA) at week 8, which is an overall assessment of the degree of the inflammatory and non-inflammatory lesion. The secondary outcomes include IGA, the total facial lesion count (Total Lesion Count), the acne-specific quality of life, etc at weeks 8 and 12. The Expectation and Credibility of treatment rating scale will be used to measure the patients' attitudes to acupuncture after the first treatment. Adverse events will also be recorded. DISCUSSION: This study is helpful to evaluate the feasibility, preliminary efficacy, and safety of SSGA in the treatment of gastrointestinal damp-heat acne. The results will be used in sample size calculations for subsequent large-scale studies.Trial registration: Chinese Clinical Trial Registry ChiCTR2100047363. Registered on June 13, 2021.

DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5.

Chordoma is a rare bone malignancy with a high rate of local recurrence and distant metastasis. Although DEP domain-containing protein 1B (DEPDC1B) is implicated in a variety of malignancies, its relationship with chordoma is unclear. In this study, the biological role and molecular mechanism of DEPDC1B in chordoma were explored. The function of DEPDC1B in chordoma cells was clarified through loss-of-function assays in vitro and in vivo. Furthermore, molecular mechanism of DEPDC1B in chordoma cells was recognized by RNA sequencing and Co-Immunoprecipitation (Co-IP) assay. The malignant behaviors of DEPDC1B knockdown chordoma cells was significantly inhibited, which was characterized by reduced proliferation, enhanced apoptosis, and hindered migration. Consistently, decreased expression of DEPDC1B suppressed tumor growth in xenograft mice. Mechanically, DEPDC1B affected the ubiquitination of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) through ubiquitin-conjugating enzyme E2T (UBE2T). Simultaneous downregulation of BIRC5 and DEPDC1B may exacerbate the inhibitory effects of chordoma. Moreover, BIRC5 overexpression reduced the inhibitory effects of DEPDC1B knockdown in chordoma cells. In conclusion, DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5, suggesting that it may be a promising candidate target with potential therapeutic value.

TGFB3 downregulation causing chordomagenesis and its tumor suppression role maintained by Smad7.

Chordoma is a rare bone tumor arising from notochordal remnants, but the underlying mechanism remains elusive. By integrated mRNA and microRNA analyses, we found significant downregulation of TGFB3 along with upregulation of its inhibitor, miR-29 family in chordoma comparing with notochord. Somatic copy number gains of miR-29 loci in chordoma highlighted a mechanism of inactivation of TGFB3 signaling in tumor formation. In zebrafish, knockout and knockdown homologous tgfb3 resulted in a chordoma-like neoplasm. On the other hand, Smad7 negative feedback regulation of transforming growth factor-ß (TGF-ß) signaling is retentive in chordoma cell UM-Chor1 despite its disruption in most cancer cells (e.g. A549). Therefore, contrary to other cancers, exogenous TGF-ß activated Smad7 by downregulating miR-182 and inhibited cell migration and invasion in UM-Chor1. Meanwhile, TGF-ß decreased chordoma characteristic protein Brachyury. Altogether, downregulation of TGFB3 causes chordomagenesis, showing a feasible target for therapies. The retention of Smad7 negative regulation may maintain the suppressor role of TGF-ß in chordoma.

High Copy-Number Variation Burdens in Cranial Meningiomas From Patients With Diverse Clinical Phenotypes Characterized by Hot Genomic Structure Changes.

Meningiomas, as the most common primary tumor of the central nervous system, are known to harbor genomic aberrations that associate with clinical phenotypes. Here we performed genome-wide genotyping for cranial meningiomas in 383 Chinese patients and identified 9,821 copy-number variations (CNVs). Particularly, patients with diverse clinical features had distinct tumor CNV profiles. CNV burdens were greater in high-grade (WHO grade II and III) samples, recurrent lesions, large tumors (diameter >4.3 cm), and those collected from male patients. Nevertheless, the level of CNV burden did not relate to tumor locations, peritumoral brain edema, bone invasion, or multiple lesions. Overall, the most common tumor CNVs were the copy-number gain (CNG) at 22q11.1 and the copy-number losses (CNLs) at 22q13.2, 14q11.2, 1p34.3, and 1p31.3. Recurrent lesions were featured by the CNLs at 1p31.3, 6q22.31, 9p21.3, and 11p12, and high-grade samples had more CNVs at 4q13.3 and 6q22.31. Meanwhile, large tumors were more likely to have the CNVs at 1p31.3 and 1p34.3. Additionally, recurrence prediction indicated the CNLs at 4p16.3 (p = 0.009, hazard ratio = 5.69) and 10p11.22 (p = 0.037, hazard ratio = 4.53) were candidate independent risk factors.

Natural Growth Dynamics of Untreated Skull Base Chordomas In Vivo.

OBJECTIVE: To study the natural growth dynamics of skull base chordomas. METHODS: A retrospective study of skull base chordomas was performed. Patients with ≥2 preoperative magnetic resonance (MR) images and with pathologically confirmed chordomas were enrolled. All clinical data and MR images were studied. RESULTS: Twenty-one patients with pathologically confirmed skull base chordomas were enrolled. The mean volume of the tumors at diagnosis was 19.9 ± 17.0 cm3, with a mean interval examination period of 22.4 ± 26.1 (range, 3-113) months. The mean tumor volume change was approximately 15.4 ± 16.3 cm3. The mean specific growth rate was 8% ± 9% per month, and the mean specific growth volume was 0.8 ± 0.7 cm3 per month. The tumor MR signal index grade, female gender, no dura mater breakthrough, endophytic type, small tumors, and soft tumor texture were related to a higher tumor growth rate (P < 0.05), and small tumors showed the greatest growth rate compared with the middle-sized and large tumors. Curve estimation was performed using a power function (R2 = 0.545). CONCLUSIONS: The skull base chordoma is a slow-growing tumor. The cases involving characteristics of female gender, endophytic type, small tumor size, and MR grade 3 showed a higher growth rate.

Radiomic signature: A novel magnetic resonance imaging-based prognostic biomarker in patients with skull base chordoma.

BACKGROUND AND PURPOSE: We used radiomic analysis to establish a radiomic signature based on anatomical magnetic resonance imaging (MRI) sequences and explore its effectiveness as a novel prognostic biomarker for skull base chordoma (SBC). MATERIALS AND METHODS: In this retrospective study, radiomic analysis was performed using preoperative axial T1 FLAIR, T2-weighted, and enhanced T1 FLAIR from a single hospital. The primary clinical endpoint was progression-free survival. A total of 1860 3-D radiomic features were extracted from manually segmented region of interest. Pearson correlation coefficient was used for feature dimensional reduction and a ridge regression-based Cox proportional hazards model was used to determine a radiomic signature. Afterwards, radiomic signature and nine other potential prognostic factors, including age, gender, histological subtype, dural invasion, blood supply, adjuvant radiotherapy, extent of resection, preoperative KPS, and postoperative KPS were analyzed to build a radiomic nomogram and a clinical model. Finally, we compared the nomogram with each prognostic factor/model by DeLong's test. RESULTS: A total of 148 SBC patients were enrolled, including 64 with disease progression. The median follow-up time was 52 months (range 4-122 months). The Harrell's concordance index of the radiomic signature was 0.745 (95% CI, 0.709-0.781) for the validation cohort, and its discrimination accuracy in predicting progression risk at 5 years in the same cohort was 82.4% (95% CI, 72.6-89.7%). CONCLUSIONS: The radiomics is a low-cost, non-invasive method to predict SBC prognosis preoperatively. Radiomic signature is a potential prognostic biomarker that may allow the individualized evaluation of patients with SBC.

Radiomic analysis of multiparametric magnetic resonance imaging for differentiating skull base chordoma and chondrosarcoma.

PURPOSE: Patients with skull base chordoma and chondrosarcoma have different prognoses and are not readily differentiated preoperatively on imaging. Multiparametric magnetic resonance imaging (MRI) is a routine diagnostic tool that can noninvasively characterize the salient characteristics of tumors. In the present study, we developed and validated a preoperative multiparametric MRI-based radiomic signature for differentiating these tumors. METHOD: This retrospective study enrolled 210 patients and consecutively divided them into the primary and validation cohorts. A total of 1941 radiomic features were acquired from preoperative T1-weighted imaging, T2-weighted imaging and contrast-enhanced T1-weighted imaging for each patient. The most discriminative features were selected by minimum-redundancy maximum-relevancy and recursive feature elimination algorithms in the primary cohort. The multiparametric and single-sequence MRI signatures were constructed with the selected features using a support vector machine model in the primary cohort. The ability of the novel radiomic signatures to differentiate chordoma from chondrosarcoma were assessed using receiver operating characteristic curve analysis in the validation cohort. RESULTS: The multiparametric radiomic signature, which consisted of 11 selected features, reached an area under the receiver operating characteristic curve of 0.9745 and 0.8720 in the primary and validation cohorts, respectively. Moreover, compared with each single-sequence MRI signature, the multiparametric radiomic signature exhibited better classification performance with significant improvement (p <  0.05, Delong's test) in the primary cohorts. CONCLUSION: By combining features from three MRI sequences, the multiparametric radiomics signature can accurately and robustly differentiate skull base chordoma from chondrosarcoma.

High Expression of TGF-ß1 Predicting Tumor Progression in Skull Base Chordomas.

OBJECTIVE: To investigate the expression characteristics and prognostic value of transforming growth factor ß1 (TGF-ß1) in primary skull base chordomas (SBCs). METHODS: The mRNA expression levels of TGF-ß1 were measured in 57 frozen samples from patients with primary SBCs. Clinical data collection, follow-up, correlations, and survival analyses were performed. RESULTS: In the series of 57 patients (29 men and 28 women) with primary SBCs, the mean value of TGF-ß1 mRNA was 1.713 with a median of 0.904. Twenty-four SBCs were soft type and 33 were hard type. The Mann-Whitney U test revealed that the expression level of TGF-ß1 mRNA in hard type SBCs was significantly higher than the expression level found in the soft type (P = 0.03). The independent-samples median test suggested that the expression level of TGF-ß1 mRNA in female patients' SBCs was significantly higher than that in male patients' SBCs (P = 0.01). Expression differences of TGF-ß1 were not seen among different pathological subtypes, tumor blood supply, or degree of resection. The Spearman rank correlation coefficient clarified that TGF-ß1 mRNA levels were not correlated with tumor diameter, preoperative Karnofsky Performance Status (KPS), postoperative KPS, follow-up KPS, age, or intraoperative blood loss. The multivariate Cox analysis revealed that pathological subtype (P = 0.008), expression level of TGF-ß1 mRNA (P = 0.01), and tumor texture (P = 0.03) were all independent prognostic factors for tumor progression. CONCLUSIONS: SBCs in female patients and SBCs with hard texture were prone to have high TGF-ß1 mRNA expression. High expression of TGF-ß1, hard tumor texture, and conventional subtype were all independent risk factors for tumor progression.

Low Transforming Growth Factor-ß3 Expression Predicts Tumor Malignancy in Meningiomas.

OBJECTIVE: We sought to clarify the expression characteristics and prognostic significance of transforming growth factor (TGF)-ß3 in cranial meningiomas. METHODS: We analyzed the expression of TGF-ß3 at the mRNA level in 38 frozen meningioma samples. Clinical data collection, follow-up, correlations, and survival analyses were performed. RESULTS: World Health Organization (WHO) grade I meningiomas showed an average expression level of 2.55, which was higher than that of WHO grade II (average of 1.50) and WHO grade III (average of 0.21) (Kruskal-Wallis test, P = 0.008). For meningiomas with a history of surgery, the mean TGF-ß3 expression level was 0.71, much lower than that of primary meningiomas with a mean value of 2.55 (Mann-Whitney U-test, P = 0.008). According to the Kaplan-Meier analysis and univariate Cox analysis, WHO grade (P = 0.001), history of surgery (P < 0.001), tumor volume (P = 0.045), preoperative Karnofsky Performance Status (P = 0.001), peritumoral brain edema (P = 0.039), postoperative radiotherapy (P = 0.001), degree of resection (P = 0.039), and TGF-ß3 expression (P = 0.038) were prognostic factors for tumor recurrence. In addition, WHO grade (P < 0.001), history of surgery (P < 0.001), preoperative Karnofsky Performance Status (P = 0.002), peritumoral brain edema (P = 0.006), postoperative radiotherapy (P = 0.007), bone invasion (P = 0.03), and TGF-ß3 expression (P = 0.041) were prognostic factors for mortality. CONCLUSIONS: TGF-ß3 expression levels gradually declined with the increase of WHO grade and were lower in recurrent meningiomas than in primary meningiomas. Besides, low TGF-ß3 expression was found to predict tumor recurrence and mortality in meningiomas based on univariate analysis.

High expression of survivin independently correlates with tumor progression and mortality in patients with skull base chordomas.

OBJECTIVE: The object of this study was to clarify the expression characteristics and prognostic value of survivin in skull base chordomas. METHODS: In this retrospective study, the authors measured the expression of survivin at the mRNA level in 81 samples from 71 patients diagnosed with skull base chordomas at their hospital in the period from July 2005 to January 2015. Clinical data collection, follow-up, and survival analyses were performed, and correlations were analyzed. RESULTS: Of the 71 patients, 50 had primary chordomas with a mean survivin expression level of 1.09; the other 21 patients had recurrent chordomas with a mean survivin expression level of 2.57, which was 2.36 times higher than the level in the primary chordoma patients (p < 0.001, Mann-Whitney U-test). In addition, an analysis of 18 paired samples derived from 9 patients showed that the expression level of survivin was 2.62 times higher in recurrent tumors than in primary tumors (p = 0.002, paired t-test). The Spearman rank correlation coefficient method showed that the expression level of survivin was positively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T1-weighted sequences (RT1; rs = 0.274, p = 0.021) and was negatively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T2-weighted sequences (RT2; rs = -0.389, p = 0.001). A multivariate Cox proportional-hazards model suggested that pathology (p = 0.041), survivin expression level (p = 0.018), preoperative Karnofsky Performance Status (KPS; p = 0.012), and treatment history (p = 0.009) were independent prognostic factors for tumor progression. Survivin expression level (p = 0.008), preoperative KPS (p = 0.019), tumor diameter (p = 0.027), and intraoperative blood loss (p = 0.015) were independent prognostic factors for death. CONCLUSIONS: Survivin expression level and preoperative KPS were independent significant prognostic factors for tumor progression and death in skull base chordoma patients. Recurrent skull base chordomas and chordomas with high RT1 and low RT2 were likely to have high survivin expression. Other independent risk factors related to tumor progression included conventional pathology and treatment history, whereas additional mortality-related risk factors included larger tumor diameter and greater intraoperative blood loss.

Identification of the Different Roles and Potential Mechanisms of T Isoforms in the Tumor Recurrence and Cell Cycle of Chordomas.

PURPOSE: The roles of T (brachyury) isoforms in chordomas remain unclear. This study aimed to investigate the different roles and mechanisms of them in chordomas. PATIENTS AND METHODS: The expression of T isoforms mRNAs in 57 chordomas was assessed, and a prognosis analysis was conducted. Cell apoptosis, proliferation and cell cycle assays were performed after specific T isoform mRNA knockdown. Whole-transcriptome sequencing, Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and competing endogenous RNA (ceRNA) analysis were conducted. RESULTS: As revealed in this study, the T-long isoform was a significant risk factor (hazard ratio [HR], 1.09; P=0.018) and the T-short isoform was a protective factor (HR, 0.24; P=0.012) associated with tumor recurrence. After T-long isoform knockdown, the cell cycle was arrested at G0/G1 phase and cell proliferation was significantly inhibited. A bioinformatic analysis revealed that the upregulation of H19, P21 and GADD45B; downregulation of SKP2 and CDK2; and accompanying changes in the P53 signaling pathway consistently contributed to G0/G1 arrest. After T-short isoform knockdown, the cell cycle was arrested at G2/M phase and cell apoptosis tended to increase slightly (P=0.067). The upregulation of YWHAZ and downregulation of E2F1 and its target genes might contribute to cell cycle arrest in G2/M phase and apoptosis. In addition, the ceRNA network, consisting of long noncoding RNAs, mRNAs and microRNAs, was established. CONCLUSION: The T-long isoform was a risk factor and the T-short isoform was a protective factor for chordoma recurrence. In addition, the cell cycle was the main target of T isoforms knockdown, and the changes in the downstream transcriptome may contribute to the different effects of specific T isoform knockdown on the changes in the cell cycle distributions and apoptosis and proliferation of chordoma cells.

A Novel MRI-Based Radiomics Model for Predicting Recurrence in Chordoma.

Chordoma is a rare primary malignant tumor. For evaluating the related factors of postoperative recurrence probability of chordoma before surgery, we retrospective collected 80 patients to analyze by using a novel radiomics method. A total of 620 3D imaging features used for radiomics analysis were extracted, and 5 features were selected from T2-weighted (T2-w) magnetic resonance imaging (MRI) that were most strongly associated with 4-year recurrence probability to build a radiomics signature. Verification by logistic regression classification model, the area under the receiver operating characteristic curve and accuracy was 0.8600 (95% CI: 0.7226-0.9824) and 85.00% in the training cohort, respectively, while in the validation cohort was 0.8568 (95% CI: 0.7327-0.9758) and 85.00%. Experimental results show that T2-w MRI-based radiomics signature is closely associated with the recurrence of chordoma. It is possible to prejudge the recurrence of chordoma before surgery.

Analysis of variants at LGALS3 single nucleotide polymorphism loci in skull base chordoma.

Although LGALS3 has been widely studied, the genotypes of the LGALS3 single nucleotide polymorphism (SNP) loci in skull base chordoma (SBC) have been not well defined. The aim of the current study was to analyze two LGALS3 SNP genotypes in patients with SBC. A total of 48 patients with SBC who underwent surgical treatment in Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University (Beijing, China) and 66 healthy participants were included in the present study. A total of two SNPs (LGALS3+191 C>A and LGALS3 +292 A>C) were selected for sequencing analysis of amplified target fragments from DNA that was extracted from blood samples. The clinical features of the patients were recorded, follow-up was conducted and statistical analysis was performed with SPSS 20.0. There were no differences in age and sex between the patients and control group. In addition, there were no significant differences in the distribution of genotypes (P=0.662) and allelic frequencies (P=0.638) at LGALS3+191 C>A between the two groups. However, significant difference was observed in the allelic distributions at LGALS3 +292 A>C between them (P=0.016), and allele A was associated with the occurrence of SBC. The distribution of the genotypes at LGALS3 +292 A>C was not significantly different in the additive model (CC vs. AC vs. AA, P=0.083) but was significantly different in the dominant model (CC+AC vs. AA, P=0.043). In the Kaplan-Meier analysis, there were no significant differences in the overall survival and progression analysis between different genotypes at LGALS3 +191 C>A (P=0.168 and P=0.120) in patients with SBC. There was no significant difference in overall survival was observed between the genotypes at +292 A>C (P=0.595). However, the progression-free survival (PFS) time of the CC+AC genotype group was longer compared with the AA genotype group (P<0.001). In the univariate and multivariate analysis of tumor progression, PFS was shorter in the AA genotype group compared with the CC+AC genotype group (P<0.001). The allele A and AA genotype at LGALS3 +292 A>C were observed to be associated with a higher risk of SBC, and the AA genotype at +292 A>C was associated with a shorter PFS time.

Surgical Management and Outcomes of Intracranial Chondromas: a Single-Center Case Series of 66 Patients.

OBJECTIVE: Management of intracranial chondromas (ICDs) is difficult. This study aims to propose a tailored management strategy based on our management of ICDs. METHODS: A retrospective review was performed in 66 patients who received surgical operations at our institute. Clinical charts and radiographs were reviewed, follow-up was performed, and adverse factors for progression-free survival (PFS) and overall survival were evaluated. RESULTS: The preoperative and postoperative Karnofsky performance status was 81.8 and 72.3, respectively. The mean tumor size was 3.5 cm. Gross total resection was achieved in 15 patients (22.7%). Six patients (10.3%) received postoperative radiation. After a mean follow-up duration of 85.5 months, recurrence occurred to 15 patients (28.8%) with surgery alone, and no recurrence was observed in patients receiving postoperative radiotherapy. Six patients (10.3%) died due to tumor progression. The risk factors affecting the PFS included age <33 years (hazard rate [HR] 6.876; 95% confidence interval [CI] 1.599-29.560; P = 0.010), tumor size ≥3.1 cm (HR 6.138; 95% CI 1.259-29.926; P = 0.025), tumor with evident atypia/mitotic activity (HR 4.672; 95% CI 1.352-16.152; P = 0.015), and partial resection (HR 12.841; 95% CI 3.004-54.896; P = 0.001). In all patients, the PFS rate was 75% at 5 years and 64% at 10 years; in addition, the overall survival rate was 93% at 5 years and 83% at 10 years. CONCLUSIONS: The therapeutic strategy for ICDs should be individualized and should consider preoperative variables. Gross total resection was attempted if the tumors were resectable; otherwise, subtotal resection was an alternative. In patients with partial resection and evident atypia/mitotic activity, consultation with an oncologist for radiotherapy was recommended.

Effect comparisons among treatment measures on progression-free survival in patients with skull base chordomas: a retrospective study of 234 post-surgical cases.

BACKGROUND: Skull base chordoma (SBC) is a rare and refractory tumor with a high rate of relapse. We aimed to investigate the relationships between different treatment measures and progression-free survival (PFS) outcomes. METHODS: Data from 234 SBC patients from one institution were retrieved from a prospectively maintained database. After grouping, the clinicopathological features and mean estimated PFS times were subject to inter-group and intra-group comparisons, and prognostic factors of PFS were estimated by statistical analyses. Two typical primary patients who suffered from repeated tumor relapses are described. RESULTS: In addition to pathological subtype (p = 0.005), the initial treatment measure for the primary cases (n = 180) was identified as an independent factor of tumor progression (p = 0.002). The patients with gross total resection exhibited the best mean estimated PFS time (109.5 months). Patients with intralesional resection exhibited the shortest PFS time (38.3 months), with an almost significant difference (p = 0.058) compared to those with adjuvant radiotherapy following intralesional resection (56.6 months). For the recurrent group (n = 54), marginal resection (p = 0.007) and adjuvant radiotherapy (p = 0.041) were confirmed as independent protective factors for PFS. The longest mean PFS time (60.3 months) was noted in those patients who received marginal resection followed by adjuvant radiotherapy. CONCLUSIONS: Treatment measures were crucial for post-surgical tumor progression in both primary and recurrent cases. For primary cases, gross total resection and adjuvant radiotherapy offered more PFS benefits to all patients and those who underwent intralesional resection. Marginal resection and adjuvant radiotherapy, which are proposed as a general treatment paradigm for primary tumors, were also equally effective when applied to relapsing tumors.

Expression of Cathepsin K in Skull Base Chordoma.

OBJECTIVE: The aim of this study was to explore the association between cathepsin K and the clinical characteristics of skull base chordoma (SBC). METHODS: This study included 58 paraffin-embedded samples and 85 frozen samples of 94 patients. All clinical data corresponding to these patients were available. Immunohistochemical staining and quantitative real-time polymerase chain reaction were performed. Positive rate of immunohistochemical staining slices and delta cycle threshold value of quantitative real-time polymerase chain reaction represented the cathepsin K expression level in protein and gene level separately. RESULTS: In protein level, expression level (EL) of invasive tumors was increased compared with noninvasive tumors (P = 0.006), EL of tumors with dura erosion was increased compared with tumors without dura erosion (P = 0.001). Tumors with septa exhibited increased EL compared with tumors without septa (P = 0.001). Tumors with lobulation exhibited increased EL compared with tumors without lobulation (P = 0.000). Higher EL of cathepsin K was associated with reduced progression-free survival (PFS) (P = 0.015). In gene level, tumors with septa showed higher EL than tumors without septa (P = 0.015), and tumors with lobulation showed higher EL than tumors without lobulation (P = 0.049). Cathepsin K EL was an independent risk factor for reduced PFS, and an increased level of cathepsin K in SBC was associated with reduced PFS (P = 0.042). CONCLUSIONS: Increased cathepsin K expression in SBC was associated with tumor invasion and reduced PFS. The cathepsin K level in SBC also was associated with tumor stage, tumor lobulation, and septa.

Clinical features and surgical outcomes of patients with skull base chordoma: a retrospective analysis of 238 patients.

OBJECTIVE Skull base chordoma is relatively rare, and a limited number of reports have been published regarding its clinical features. Moreover, the factors associated with extent of resection, as well as the value of marginal resection for long-term survival, are still in question for this disease. The objective of this study was to investigate these factors by evaluating their clinical features and surgical outcomes. METHODS A retrospective analysis of 238 patients with skull base chordomas, who met the inclusion criteria, was performed. This study summarized the clinical features, selection of approaches, degree of resection, and postoperative complications by statistical description analyses; proposed modified classifications of tumor location and bone invasion; studied the contributions of the clinical and radiological factors to the extent of resection by Pearson χ2, ANOVA, rank test, and binary logistic regression analysis; and estimated the differences in overall survival and progression-free survival rates with respect to therapeutic history, classification of tumor location, extent of bone invasion, and extent of tumor resection by the Kaplan-Meier method. A p value < 0.05 was considered statistically significant. RESULTS The study included 140 male and 98 female patients with a mean age of 38.1 years. Headache and neck pain (33.2%) and diplopia (29%) were the most common initial symptoms. Sphenoclival type accounted for the largest proportion of tumor location (59.2%); endophytic chordoma was the more common type of bone invasion (81.5%). Lateral open approaches were performed in two-thirds of the study population (78.6%). The rate of marginal resection was 66%, composed of gross-total resection (11.8%) and near-total resection (54.2%). Meningitis (8%) and CSF leakage (3.8%) were the most frequent complications. The mean follow-up period was 43.7 months. The overall survival and progression-free survival rates at 5 years were 76% and 45%, respectively. Recurrent tumor and larger tumor volume (≥ 40 cm3) were identified as risk factors of marginal resection. Patients who presented with recurrent tumor and underwent intralesional resection had a worse long-term outcome. CONCLUSIONS The classifications of both tumor location and bone invasion demonstrated clinical value. Marginal resection was more likely to be achieved for primary lesions with smaller volumes (< 40 cm3). The rate of CSF leakage declined due to improved dura mater repair with free fat grafts. Marginal resection, or gross-total resection when possible, should be performed in patients with primary chordomas to achieve better long-term survival.